Synthesis of N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)[carbonyl-11C]acetamide ([carbonyl-11C]DAA1106) and analogues using [11C]carbon monoxide and palladium(0) complex

✍ Scribed by Obaidur Rahman; Bengt Långström

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 137 KB
• Volume: 50
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1437

✦ Synopsis

Abstract

N‐(2,5‐Dimethoxybenzyl)‐N‐(5‐fluoro‐2‐phenoxyphenyl)acetamide (DAA1106), a potent and selective ligand for peripheral benzodiazepine receptor, and eight structurally related analogues were labelled with ^11^C at the carbonyl position using a low concentration of [^11^C]carbon monoxide and the micro‐autoclave technique. A combinatorial approach was applied to synthesize the analogues using similar reaction conditions. Palladium‐mediated carbonylation using tetrakis(triphenylphosphine)palladium, various amines and methyl iodide or iodobenzene was employed in the synthesis. The ^11^C‐labelled products were obtained with 10–55% decay‐corrected radiochemical yields and the final product was more than 97% pure in all cases. Specific radioactivity was determined for the compound [carbonyl‐^11^C]DAA1106 using a single experiment and a 10‐µA h bombardment. The specific radioactivity, measured 36 min after end of bombardment, was 455 GBq/µmol. Synthetic routes to the precursors and reference compounds were also developed. The presented approach is a novel method for the synthesis of [carbonyl‐^11^C]DAA1106 and its analogues, and allows the formation of a library of ^11^C‐labelled DAA1106 analogues which can be used to optimize the performance as a potential positron emission tomography tracer. Copyright © 2007 John Wiley & Sons, Ltd.